Donor specific unresponsiveness to organ allografts remains an elusive goal in clinical transplantation, as most successful experimental protocols for the induction of allograft tolerance require lengthy pretreatment. The use of an induction course of antilymphocyte (ALS) followed by the transfusion of the recipient of donor bone marrow, has been shown to induce prolonged allograft survival and is applicable to use in clinical cadaver organ transplantation. Our preliminary data in humans support that the transfusion of cryopreserved marrow following a course of ALS is safe and without major side effects. Twenty patients have been included in the protocol and all 20 have been discharged with functioning allografts. Eight of these have been withdrawn from all prednisone (length of follow-up 2.g months). The primary purpose of this project will be to better define the optimal use of donor bone marrow as a specific antigen in the induction of transplantation tolerance. The human trial will be continued. Cellular immune responsiveness will be monitored by serial MLC and the presence of peripheral chimerism will be determined by RFLP analyses. A canine model will be established to test the interaction with ALS/marrow of the commonly used pharmacologic agents. The optimal number of cells, the timing of infusion, multiple infusions and precise cell types responsible for enhanced allograft survival will be investigated.